This work aims to analyze the immunomodulatory effect of pomegranate peel polysaccharides (PPP) on the immunosuppressed mice induced by cyclophosphamide (CTX). All the mice were divided into 6 groups randomly and the immunoprophylaxis mice were administrated with PPP [100, 200, 400 mg/(kg·d)] by gavage for consecutive 28 days. The results showed that PPP can slow down the decline of body weight and increase the immune organ index of the immunosuppressed mice. Compared to the model mice, the enzymatic activity of LDH (lactate dehydrogenase) and ACP (acid phosphatase) of the mice spleen administrated with PPP by gavage was enhanced significantly. PPP stimulated proliferation and secretion of splenic lymphocytes and markedly increased the immunoglobulin (Ig-A, Ig-G and Ig-M) expression and the release of cytokines (TNF-α, IL-2 and INF-γ) in cyclophosphamide-induced immunosuppressed mice. Hepatic antioxidant enzymatic activities of T-AOC (total antioxidant capacity), T-SOD (total superoxide dismutase), GSH-PX (glutathione peroxidase) and CAT (catalase) were markedly increased when the mice were administrated with high dosage of PPP. So it can be concluded that PPP could be used as an efficacious adjacent immunopotentiating therapy or an alternative means in lessening chemotherapy-induced immunosuppression, and also can be utilized as immunostimulants for food and pharmaceutical industries.